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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The A-kinase anchoring protein Yotiao binds and regulates adenylyl cyclase in brain
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The A-kinase anchoring protein Yotiao binds and regulates adenylyl cyclase in brain

机译：A激酶锚蛋白Yotiao结合并调节大脑中的腺苷酸环化酶

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摘要

A-kinase anchoring proteins (AKAPs) influence the spatial and temporal regulation of cAMP signaling events. Anchoring of PKA in proximity to certain adenylyl cyclase (AC) isoforms is thought to enhance the phosphorylation dependent termination of cAMP synthesis. Using a combination of immunoprecipitation and enzy-mological approaches, we show that the plasma membrane targeted anchoring protein AKAP9/Yotiao displays unique specificity for interaction and the regulation of a variety of AC isoforms. Yotiao inhibits AC 2 and 3, but has no effect on AC 1 or 9, serving purely as a scaffold for these latter isoforms. Thus, Yotiao represents an inhibitor of AC2. The N terminus of AC2 (AC2-NT), which binds directly to amino acids 808-957 of Yotiao, mediates this interaction. Additionally, AC2-NT and Yotiao (808-957) are able to effectively inhibit the association of AC2 with Yotiao and, thus, reverse the inhibition of AC2 by Yotiao in membranes. Finally, disruption of Yotiao-AC interactions gives rise to a 40% increase in brain AC activity, indicating that this anchoring protein functions to directly regulate cAMP production in the brain.
机译：A激酶锚定蛋白（AKAP）影响cAMP信号转导事件的时空调节。人们认为将PKA锚定在某些腺苷酸环化酶（AC）同工型附近可以增强cAMP合成的磷酸化依赖性终止。使用免疫沉淀和酶学方法的组合，我们表明靶向质膜的锚定蛋白AKAP9 / Yotiao对相互作用和多种AC同种型的调节显示出独特的特异性。 Yotiao抑制AC 2和3，但对AC 1或9没有影响，仅用作这些亚型的支架。因此，Yotiao代表AC2的抑制剂。直接与Yotiao的氨基酸808-957结合的AC2的N末端（AC2-NT）介导了这种相互作用。另外，AC2-NT和Yotiao（808-957）能够有效抑制AC2与Yotiao的缔合，从而逆转Yotiao在膜中对AC2的抑制。最后，Yotiao-AC相互作用的破坏使大脑AC活动增加了40％，这表明这种锚定蛋白的功能是直接调节大脑中cAMP的产生。

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